Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our recent analysis of gene expression led to the identification of several genes in endothelial cells that line tumor blood vessels. The products of these genes are of particular interest because they reside on the cell surface and may therefore be directly accessible to blood-borne therapeutics. In an attempt to understand their functional role in angiogenesis, we have begun to generate conditional knockouts for three new tumor endothelial markers. To probe the function of these genes specifically in endothelial cells and to avoid potential embryonic lethality if necessary, we generated conditional lox-p flanked floxed alleles. By challenging gene disrupted mice with tumors, we hope to determine if any of these genes are critical for tumor angiogenesis. The studies should also allow us to better understand the normal physiological function of these genes.